1. Field
The following description is related to a process for the purification of idraparinux sodium, i.e., nonasodium methyl 2,3,4-tri-O-methyl-6-O-sulfonato-α-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-β-D-glucopyranuronosyl-(1→4)-2,3,6-tri-O-sulfonato-α-D-glucopyranosyl-(1→4)-2,3-di-O-methyl-α-L-idopyranuronosyl-(1→4)-2,3,6-tri-O-sulfonato-α-D-glucopyranoside.
2. Background
Idraparinux sodium is an anticoagulant medication chemically related to low molecular weight heparins. Idraparinux sodium is a synthetic pentasaccharide Factor Xa inhibitor and has been used as an anticoagulant and antithrombotic medication. One feature of idraparinux sodium over low-molecular-weight heparin (LMWH) or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) may be substantially lower for treatments utilizing idraparinux sodium.
Idraparinux sodium has a chemical structure similar to, and a method of action substantially the same as, fondaparinux, an LMWH. However, idraparinux sodium has an elimination half-life of about five to about six times longer than fondaparinux (e.g., the half-life of idraparinux sodium is approximately 80 hours while that of fondaparinux is about 17 hours). Because of the long half-life, idraparinux sodium may be injected into a patient only once per week.
The structure of idraparinux sodium may be illustrated as follows:

Idraparinux sodium may be synthesized via a [4+1] strategy as disclosed in U.S. Pat. No. 6,174,863 B1 and EP0454220B1, or via a [3+2] strategy as disclosed by Herczeg (Herczeg Mihály, “Novel Syntheses of Idraparinux, the Anticoagulant Pentasaccharide with Indirect Selective Factor Xa Inhibitory Activity”, Tetrahedron, 2013, 69(15): 3149-3158) and Yu (Yu B. and Chen C., “Efficient Synthesis of Idraparinux, the anticoagulant pentasaccharide”, Bioorganic & Medicinal Chemistry Letters, 2009, 19(14): 3875-3879).
The idraparinux sodium synthesized according to the above-identified methods contains impurities, such as organic impurities (e.g., carboxyl group containing and sulfonic group containing salts, such as disaccharide and trisaccharide isomers, triethylamine salt, etc.), and inorganic impurities (e.g., sodium acetate, sulfate salt, etc.).
The purity of the synthesized idraparinux sodium (i.e., the crude idraparinux sodium) obtained utilizing these methods is only about 60% to about 70%, which does not meet certain requirements for active pharmaceutical ingredients (API) for the pharmaceutical industry (i.e., an API purity of about 99%).